Transcripts of the cellular c-Ha-ras are increased during liver regeneration and at certain stages in diet-induced hepatocarcinogenesis in rats. C-Ha-ras is the cellular homologue of the transforming gene of Harvey murine sarcoma virus. In liver regeneration, induced by either partial hepatectomy or carbon tetrachloride injury, a 2-4 fold increase in the levels of c-Ha-ras mRNA coincides with the activation of DNA synthesis followed by rapid (within 24 hours) return to normal levels. In prenoeplastic livers of rats fed a diet deficient in choline and containing 0.1% ethionine there is a dramatic increase in the level of c-Ha-ras mRNA at 4-6 weeks followed by an equally rapid decrease by 8 weeks although the levels remain higher than normal. Since we have identified two cases where transcripts of a cellular oncogene are transiently elevated, we have a good experimental system to: a) define the expression of both members of the ras family (c-Ki-ras and c-Ha-ras) and to ask which of the multiple copies of these genes are normally transcribed and which are transiently activated; b) determine if chemicals which act as liver carcinogens, only if given during regeneration, modify the pattern of expression of the ras genes during liver regeneration in the rat; c) determine if the transient elevation of ras transcripts can be correlated with changes in methylation patterns and DNase I hypersensitivity of the ras locus; d) determine if DNA from normal, regenerating, MNU-treated regenerating and 4-6 week preneoplastic rat liver contain transforming DNA which can be identified by the NIH 3T3 transfection assay.